This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of the projects is to study the crystal structure of the enzymes from the pathway of folate biosynthesis and nucleoside salvage in Mycobacterial tuberculosis, an opportunistic pathogen that causes TB and to develop these enzymes as therapeutic targets to treat TB. We have obtained crystals of some the key enzymes in these pathways, including dihydrofolate reductase and adenosine kinase in complexes with their substrate or substrate analogs. The crystal structure of the protein complexes will provide the molecular basis for developing novel compounds that are highly potent and selective against M. tuberculosis and are potentially useful for the TB treatment.